SUMMARY: Background Mutation of the growth factor-independent 1B (GFI1B) fifth DNA-binding zinc-finger domain causes macrothrombocytopenia and α-granule deficiency leading to clinical bleeding. The phenotypes associated with GFI1B variants disrupting non-DNA-binding zinc-fingers remain uncharacterized. Objectives To determine the functional and phenotypic consequences of GFI1B variants disrupting non-DNA-binding zinc-finger domains. Methods The GFI1B C168F variant and a novel GFI1B c.2520 + 1_2520 + 8delGTGGGCAC splice variant were identified in four unrelated families. Phenotypic features, DNA-binding properties and transcriptional effects were determined and compared with those in individuals with a GFI1B H294 fs mutation of the fifth DNA-binding zinc-finger. Patient-specific induced pluripotent stem cell (iPSC)-derived megakaryocytes were generated to facilitate disease modeling. Results The DNA-binding GFI1B variant C168F, which is predicted to disrupt the first non-DNA-binding zinc-finger domain, is associated with macrothrombocytopenia without α-granule deficiency or bleeding symptoms. A GFI1B splice variant, c.2520 + 1_2520 + 8delGTGGGCAC, which generates a short GFI1B isoform that lacks non-DNA-binding zinc-fingers 1 and 2, is associated with increased platelet CD34 expression only, without quantitative or morphologic platelet abnormalities. GFI1B represses the CD34 promoter, and this repression is attenuated by different GFI1B zinc-finger mutations, suggesting that deregulation of CD34 expression occurs at a direct transcriptional level. Patient-specific iPSC-derived megakaryocytes phenocopy these observations. Conclusions Disruption of GFI1B non-DNA-binding zinc-finger 1 is associated with mild to moderate thrombocytopenia without α-granule deficiency or bleeding symptomatology, indicating that the site of GFI1B mutation has important phenotypic implications. Platelet CD34 expression appears to be a common feature of perturbed GFI1B function, and may have diagnostic utility.
OBJECTIVE: This study focused on designing a serious game as an experimental program to prevent and control health rumors. The focus of the study was explicitly on the context of the social networking service for midelders/elders.
METHODS: This research involved 2 major parts: adopting the Transmission Control Protocol model for games and then, based on the model, designing a game named "Fight With Virus" as an experimental platform and developing a cognitive questionnaire with a 5-point Likert scale. The relevant variables for this experimental study were defined, and 10 hypotheses were proposed and tested with an empirical study. In total, 200 participants were selected for the experiments. By collecting relevant data in the experiments, we conducted statistical observations and comparative analysis to test whether the experimental hypotheses could be proved.
RESULTS: We noted that compared to traditional media, serious games are more capable of inspiring interest in research participants toward their understanding of the knowledge and learning of health commonsense. In judging and recognizing the COVID-19 health rumor, the test group that used game education had a stronger ability regarding identification of the rumor and a higher accuracy rate of identification. Results showed that the more educated midelders/elders are, the more effective they are at using serious games.
CONCLUSIONS: Compared to traditional media, serious games can effectively improve midelders'/elders' cognitive abilities while they face a health rumor. The gameplay effect is related to the individual's age and educational background, while income and gender have no impact.